Isaria cicadae Miquel prevents intestinal fibrosis by activating transforming growth factor-β1 signaling to regulate the balance between matrix metalloproteinases and tissue inhibitors of metalloproteinase 1 in mice with Crohn’s disease

Abstract

We aim at exploring the potential therapeutic effect and mechanisms of artificial Isaria cicadae Miquel (IcM) in Crohn’s disease (CD)-related intestinal fibrosis. The Crohn's fibrosis model was induced by Trinitrobenzene sulphonic acid (TNBS). Mice were divided into control group, TNBS control group, and IcM treatment group (H, M, D). After four weeks, the entire length of the colon and serum were collected, and Hematoxylin and Eosin staining and Masson’s collagen trichrome staining were performed for determining the colon histological score. The contents of TGF-β1, CTGF, and IFN-γ were determined by ELISA. FN and α-SAM were evaluated by Western blotting; further, MMP-1, MMP-3, and TIMP-1 mRNA were determined by qRT-PCR. We observed that IcM prevents intestinal fibrosis in mice with CD. In addition, IcM was capable of significantly down-regulating the expression of major fibrosis markers (⍺-SMA and fiber-fibroin) and key fibrogenic molecules TGF-β1 and CTGF, and promoting the expression of IFN-γ, which has antifibrotic effects to maintain MMP/TIMP balance.